02643nas a2200385 4500000000100000008004100001260004700042653001000089653001600099653001100115653001900126653001000145653001100155653001200166653002100178653000900199653001600208653002500224653002700249653001600276100001600292700001300308700002200321700001300343700001500356700001300371700001400384700001200398700001400410245010000424300001100524490000800535520170000543022001402243 2012 d c2012 MaybBlackwell Publishing LtdaOxford10aAdult10aCoinfection10aFemale10aHIV Infections10aHIV-110aHumans10aleprosy10aLymphocyte Count10aMale10aMiddle Aged10aMycobacterium leprae10aNatural Killer T-Cells10aYoung Adult1 aCarvalho KI1 aBruno FR1 aSnyder-Cappione J1 aMaeda SM1 aTomimori J1 aXavier M1 aHaslett P1 aNixon D1 aKallas EG00aLower numbers of natural killer T cells in HIV-1 and Mycobacterium leprae co-infected patients. a96-1020 v1363 a

Natural killer T (NKT) cells are a heterogeneous population of lymphocytes that recognize antigens presented by CD1d and have attracted attention because of their potential role linking innate and adaptive immune responses. Peripheral NKT cells display a memory-activated phenotype and can rapidly secrete large amounts of pro-inflammatory cytokines upon antigenic activation. In this study, we evaluated NKT cells in the context of patients co-infected with HIV-1 and Mycobacterium leprae. The volunteers were enrolled into four groups: 22 healthy controls, 23 HIV-1-infected patients, 20 patients with leprosy and 17 patients with leprosy and HIV-1-infection. Flow cytometry and ELISPOT assays were performed on peripheral blood mononuclear cells. We demonstrated that patients co-infected with HIV-1 and M. leprae have significantly lower NKT cell frequencies [median 0.022%, interquartile range (IQR): 0.007-0.051] in the peripheral blood when compared with healthy subjects (median 0.077%, IQR: 0.032-0.405, P < 0.01) or HIV-1 mono-infected patients (median 0.072%, IQR: 0.030-0.160, P < 0.05). Also, more NKT cells from co-infected patients secreted interferon-γ after stimulation with DimerX, when compared with leprosy mono-infected patients (P = 0.05). These results suggest that NKT cells are decreased in frequency in HIV-1 and M. leprae co-infected patients compared with HIV-1 mono-infected patients alone, but are at a more activated state. Innate immunity in human subjects is strongly influenced by their spectrum of chronic infections, and in HIV-1-infected subjects, a concurrent mycobacterial infection probably hyper-activates and lowers circulating NKT cell numbers.

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